Is DSG1 p.Pro871= (c.2613A>T) pathogenic?

DSG1 p.Pro871= (c.2613A>T) is classified Benign/Likely benign in DSG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.837%, afr).

How common is DSG1 p.Pro871= (c.2613A>T) in the general population?

DSG1 p.Pro871= (c.2613A>T) is rare (popmax 0.837%, afr) (gnomAD).

DSG1 p.Pro871=

c.2613A>T · rs36039798 · VCV709954

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.837%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.6
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.837% African / African-American · 628/75,046 alleles

Filtering AF 0.783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.761%

Overall 0.0432% 698/1,614,150 alleles · rare exomes 335/1,461,890 · genomes 363/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.837%	120
Remaining individualsnot grpmax-eligible	0.056%	1,786
Middle Eastern	0.0495%	2,021
Admixed American	0.0417%	2,401
South Asian	0.00329%	30,358
European (non-Finnish)	0.000339%	295,005

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSG1
Protein: p.Pro871=
Coding: c.2613A>T
MANE Select: NM_001942
dbSNP: rs36039798
Type: single nucleotide variant
Location: chr18:31354809 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93
Residue 871: a UniProt-annotated variant site (in ppks1; uncertain significance; reduces expression of krt10 in keratinocytes); a UniProt-annotated variant site (in ppks1; uncertain significance; reduces protein expression, expression of krt10 and loricrin and increases phosphorylated erk in keratinocytes); a UniProt-annotated variant site (in ppks1; uncertain significance; loss of intact desmosome cell-cell junctions and retracted keratin intermediate filaments at the cell periphery of keratinocytes in the upper spinous and granular layers)

Full DSG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSG1 p.Pro871Leu Uncertain significance ★ ⚠ same residue
DSG1 p.Arg128Ter Pathogenic ★★ same type
DSG1 p.Arg144Ter Pathogenic ★★ same type
DSG1 p.Arg219Ter Pathogenic ★★ same type
DSG1 p.Arg242Ter Pathogenic ★★ same type
DSG1 p.Arg26Ter Pathogenic ★★ same type
DSG1 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
DSG1 p.Arg887Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dsg1-p-pro871 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown